Project Summary/Abstract In utero exposure to multiple environmental chemicals has been shown to adversely impact health throughout the lifespan, leading to adverse birth outcomes, neurodevelopmental deficits, diabetes and obesity, and cancer. Yet, a key data gap limiting our ability to characterize and address developmental health risks is the lack of data on the extent to which neonates are exposed to the vast array of industrial chemicals used in the US. Over 90% of the chemicals manufactured and used in high volumes (>25,000 pounds/year) in the US are not measured in large-scale human biomonitoring studies. Further, the current biomonitoring approach requires a priori selection of compounds for which to develop and validate targeted analytical methods; the lack of data on chemical use in industrial or commercial products hinders the ability to accurately anticipate to which of the almost 8000 high use chemicals the US population is most likely exposed. To address these challenges, our project will advance an innovative, discovery-driven research project using liquid chromatography- quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) to perform a General Suspects Screen for the presence and co-occurrence of approximately 700 Environmental Organic Acids (EOAs) in a demographically diverse population of maternal-neonate pairs. We will also demonstrate how this screen can inform the selection of chemicals for targeted analysis methods development while addressing demographic disparities in EOA exposure and the extent to which maternal serum levels accurately reflect in utero exposures. We focus on EOAs because they are more easily detected by our LC-QTOF/MS and thus are a good model for our novel approach. Also, they are structurally similar to chemicals known to adversely impact development and thus are of potential health risk. Using LC-QTOF/MS, we will screen 300 matched umbilical cord and maternal serum samples, collected from a racially and economically diverse population, for ~ 700 EOAs. Using the LC- QTOF/MS results, we will identify 10 EOAs with potential for widespread human exposure and for demographic and maternal-neonatal exposure disparities. We will develop LC-MS/MS methods to confirm and quantify these 10 EOAs, and evaluate the performance of the LC-QTOF/MS screen. We will compare umbilical cord serum levels of the 10 EOAs in Hispanic versus non-Hispanic white, US? versus foreign-born, and low? versus high-income subgroups, and assess differences in exposures between maternal-fetal pairs. Our discovery-driven, suspect screen will pioneer a biomonitoring approach that prioritizes chemicals for targeted method development based on their likelihood of detection in the human population. It will also be an invaluable resource for other researchers who may query it for novel chemical exposures during the prenatal period. Finally, we will also make substantial contributions to the inventory of targeted methods for environmental chemicals and generate critical new exposure data on vulnerable and susceptible populations that is foundational to characterize and inform prevention of health risks from harmful chemicals.